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Research ArticleArticle

Enhancement of Brain Glutamate Dehydrogenase Activity and Glutamate Oxidation by Adenine Nucleotides

V. GENE ERWIN
Molecular Pharmacology November 1969, 5 (6) 615-624;
V. GENE ERWIN
School of Pharmacy, University of Colorado, Boulder, Colorado 80302
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Abstract

The rate of oxidation of glutamate by brain homogenates or mitochondria was enhanced approximately 4-fold by 5'-AMP, cyclic 3',5'-AMP, or 5'-ADP. These nucleotides were equally effective in augmenting glutamate oxidation, while 3'-AMP, 2'-AMP, and 2',3'-AMP were without effect. Cyclic 3',5'-AMP did not increase the rate of glutamate oxidation in heart or testis homogenates but produced 13% and 89% stimulation by liver and kidney homogenates, respectively. Kinetic and gel filtration evidence indicates that glutamate dehydrogenases of brain, liver, and kidney mitochondria are not identical in their properties. The enhancement of activity of the brain enzyme by 5'-AMP or cyclic 3',5'-AMP was dependent on the pH of the reaction mixture and the concentration of NAD. At pH 8.0, the apparent Km for NAD was decreased from 2 mM in the absence of adenine nucleotides to 0.4 mM or 0.5 mM in the presence of 5'-AMP or cyclic 3',5'-AMP, respectively. At pH 7.5, 5'-AMP evoked twice the stimulation produced by corresponding concentrations of cyclic 3',5'-AMP. Kinetic evidence indicates that brain glutamate dehydrogenase contains at least two cooperative sites for NAD in the absence of adenine nucleotides, and only one site in the presence of these activators. Density gradient studies suggest that the molecular weight of the activated enzyme is approximately 250,000.

  • Copyright ©, 1969, by Academic Press Inc.

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Molecular Pharmacology
Vol. 5, Issue 6
1 Nov 1969
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Research ArticleArticle

Enhancement of Brain Glutamate Dehydrogenase Activity and Glutamate Oxidation by Adenine Nucleotides

V. GENE ERWIN
Molecular Pharmacology November 1, 1969, 5 (6) 615-624;

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Research ArticleArticle

Enhancement of Brain Glutamate Dehydrogenase Activity and Glutamate Oxidation by Adenine Nucleotides

V. GENE ERWIN
Molecular Pharmacology November 1, 1969, 5 (6) 615-624;
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